The data which are collected and analyzed in the Registry provide the sole comprehensive series of cases of DES-associated clear cell adenocarcinoma (CCA) for comparative and collaborative study. The specific aims are to update and enhance the data on currently accessioned cases of CCA; to maximize ascertainment of newly diagnosed cases; to add to the Registry women who have been treated but not previously accessioned, by collaborating with the DES Cancer Network (DCN - Collaborative Project A); to monitor the development of other mullcrian-derived primary cancers, such as cancer of the fallopian tube and endometrium to detect early any increase in occurrence; to serve as a source of information for treating physicians and patients; and to serve as a collaborating resource with NCI for other approved investigators who will rely on the Registry participants and/or data for research implementation. Once an expanded cohort has been established by adding all identify new cases of documented CCA, a questionnaire (approved by the Project Steering Committee) will be applied to all study participants. This questionnaire will incorporate new data for Registry as well as for the collaborating investigations. Additional topics to be investigated include extension of the age-incidence curve of CCA to older patients, updating the survival curve and investigation of factors affecting survival and recurrence including the complications of therapy. A collaborative trial through NCI will be sought to develop an improved regimen for recurrence therapy. Two additional collaborative projects are proposed. The first is a case- control study undertaken to assess risk factors for CCA among women exposed to DES, in particular, to assess the relation of oral contraceptive use, age at menarche, height, obesity, and season of birth. In addition, epidemiologic factors that may promote recurrence of CCA, in particular, the relation of height, obesity, cigarette smoking, and estrogen replacement therapy will be investigated, with emphasis on factors that may contribute to the development of late (greater than 8 years) recurrences. The second study will be to determine if human papillomavinus and p53 tumor suppressor gene alterations, currently linked to the natural history of non-clear cell carcinoma of the vagina and cervix, and associated with CCA.